Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A "masked" Philadelphia chromosome (Ph), t(1;22;9)(p32;q11;q34), was found in the bone marrow and peripheral blood cells of a patient with chronic myeloid leukemia (CML) during the chronic and blastic phases of the disease. As an additional change, a reciprocal translocation t(12;13)(p13;q14) was observed in the blastic phase. Southern blot analysis showed a rearrangement of the breakpoint cluster region (bcr). Northern blot analysis with a c-abl probe showed an abnormal 8.5 kb c-abl RNA transcript in addition to the normal 6- and 7-kilobase (kb) c-abl species. Thus, the results demonstrate the presence of a c-abl/bcr rearrangement in the masked Ph corresponding to that observed in the standard Ph translocation t(9;22)(q34;q11) of CML.
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PMID:Cytogenetic and molecular analysis of a "masked" Philadelphia chromosome in chronic and blastic phases of chronic myeloid leukemia. 235 96

A 26-year-old man, who presented with bilateral fundal haemorrhages, was found to have chronic myeloid leukaemia (CML). The Ph chromosome was not present but a clone with t(1;9) (p32;q34) was detected. On referral for bone marrow transplant (BMT) he was found to be in accelerated phase with clonal evolution in three cell lines inv(3)(q21q26); inv(3)(q),i(17q); inv(3q)+8. Molecular investigation revealed a breakpoint on chromosome 22 within the breakpoint cluster region (bcr) similar to that found in Ph+ cases. After BMT, from an HLA-identical sister, successful engraftment (46,XX) was accompanied by evidence of a residual host cell population with further evolution (del(7)(q22)) and persistence of the bcr+ clone. Acute myeloid leukaemia, detected 5 months later, was associated with predominance of the clone 46XY,t(1;9),inv(3q),del(7)(q22) which failed to respond to treatment and the patient died 6.5 months after BMT. This case indicates that BMT, after the acquisition of additional chromosomal change in accelerated phase, may fail owing to persistence of the leukaemic clone. In addition the BMT conditioning regimen may produce further abnormalities which confer drug resistance on the persisting clone, which can emerge as an intractable myeloid blast crisis.
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PMID:Clonal evolution in Ph-negative, bcr-positive chronic myeloid leukaemia before and after bone marrow transplantation. 251 23

The standard t(9;22)(q34;q11) found in Philadelphia (Ph) chromosome positive chronic myeloid leukemia (CML) involves a highly restricted (5.8 kb) chromosome 22 breakpoint cluster region (bcr), which results in the formation of a chimeric gene comprising exons from the 5' end of bcr and protooncogene c-abl coding sequences from chromosome 9. In a survey of 21 patients with hematologic and clinical features of CML we detected rearrangement of the chromosome 22 bcr by gene probe analysis in all cases, including 16 with a standard t(9;22), two with variant Ph translocations [t(10;22)(q26;q11);t(11;22)(p15;q11)], one with a complex Ph translocation [t(9;11;22)(q34;q13;q11)], one with a complex translocation and a masked Ph[t(9;14;22) (q34;q24;q11)], and one Ph-negative case with a t(1;9)(p32;q34). These observations further substantiate the suggestion that, despite karyotypic heterogeneity, a common underlying molecular lesion, the bcr-abl gene chimera, is involved in the disease pathogenesis of CML.
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PMID:Chromosome 22 breakpoints in variant Philadelphia translocations and Philadelphia-negative chronic myeloid leukemia. 264 33

An association between myelofibrosis (MF) and chronic granulocytic leukemia (CGL) has been recognized. MF is usually a sign of a poor prognosis but its relation to other important parameters of CGL is not known. We observed a 54-year-old, white male patient who was well until May 1983 when he began developing gradually increasing right hip and left shoulder pain. Clinical evaluation 3 months later revealed splenomegaly and a white blood count of 126,000 with 29 segmented neutrophils, 22 bands, 7 metamyelocytes, 11 myelocytes, 6 promyelocytes, 5 blasts, 2 eosinophils, 5 basophils, and 3 lymphocytes. Cytogenetic analysis by G-banding technique showed a male karyotype with all 20 bone marrow cells examined positive for the Philadelphia chromosome. The patient was placed on busulfan therapy with good symptomatic improvement, but later suffered severe thrombocytopenia. At the end of October 1983, he was admitted with blast crisis and thrombocytopenia and was initiated on vincristine and cytosine arabinoside therapy. His bone marrow was repeatedly inaspirable and the biopsy was characterized by diffuse fibrosis. Chromosome analysis of 16 spontaneously dividing cells in the blood at this time revealed that 86% of cells had a karyotype of 46,XY,t(9;22)(q34;q11),t(1;3)(p32;p21) with the rest of the cells having only the Ph chromosome. The patient died 4 months later of intracranial hemorrhage. Chromosome #3 involvement has been reported in acute MF and essential thrombocytosis, but no specific cytogenetic abnormalities have been found in MF associated with CGL. It is unclear whether t(1;3) in this case represents a cytogenetic marker of MF or blast transformation, but it is certainly associated with poor prognosis and short survival.
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PMID:Possible cytogenetic marker associated with myelofibrosis in chronic granulocytic leukemia and its prognostic significance. 347 Jan 22